Electrostatics in solvation, catalysis, and enzyme evolution
Abstract/Contents
- Abstract
- The study of catalysis, whether biological or chemical, enables life on both a micro- and macroscopic level, the former controlling metabolism, the latter enabling nearly many of the advances of modern civilization. However, the underlying physics that governs these catalytic processes still remains largely a mystery. Towards that goal, enzymes have served as both an inspiration and great source material for unravelling the chemical and physical mechanisms of catalysis, exhibiting uniquely arranged 3D structures and functions that make up the canonical structure-function relationship. However, fundamental limitations in our understanding still persist as many labs working on de novo design have demonstrated the ability to construct both new and old protein architectures, but instilling function remains a fundamental challenge. Towards that goal, this thesis describes my research on elucidating the electrostatic origins of non-covalent interactions in complex environments like enzyme active sites, to better understand their structural and functional importance. As such, the vibrational Stark effect (VSE) is the hallmark and basis of most of my research as a tool to better understand environments in terms of their electrostatic components as projected along small local molecular probes, such as carbonyls. In order to utilize the VSE to its fullest, the first half of my thesis focuses on exploring and testing the fundamental spectroscopic and physical limits underlying the VSE with diverse carbonyl probes for applications such as organocatalysis, electrochemical energy storage, solvation, and enzymatic catalysis. After developing and benchmarking the VSE, I've combined this approach with biophysical characterization and mechanistic enzymology approaches to better unravel these relationships in the model enzymatic system TEM β-lactamase over its evolutionary trajectory to extended-spectrum activity and antibiotic resistance in order to disentangle the role of electrostatics in guiding enzyme evolution. This thesis expands upon our understanding of the role of electrostatics in solvation, catalysis, and enzyme evolution
Description
Type of resource | text |
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Form | electronic resource; remote; computer; online resource |
Extent | 1 online resource |
Place | California |
Place | [Stanford, California] |
Publisher | [Stanford University] |
Copyright date | 2020; ©2020 |
Publication date | 2020; 2020 |
Issuance | monographic |
Language | English |
Creators/Contributors
Author | Schneider, Samuel Hayes |
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Degree supervisor | Boxer, Steven G. (Steven George), 1947- |
Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
Thesis advisor | Kool, Eric T |
Thesis advisor | Solomon, Edward I |
Degree committee member | Kool, Eric T |
Degree committee member | Solomon, Edward I |
Associated with | Stanford University, Department of Chemistry. |
Subjects
Genre | Theses |
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Genre | Text |
Bibliographic information
Statement of responsibility | Samuel Hayes Schneider |
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Note | Submitted to the Department of Chemistry |
Thesis | Thesis Ph.D. Stanford University 2020 |
Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Samuel Hayes Schneider
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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